Systems and methods for facilitating the generation of core-sheath taylor cones in electrospinning

ABSTRACT

Systems and methods for electrospinning of core-sheath fibers are provided. The systems and methods achieve optimization of a shear stress that exists at a fluid boundary between core and sheath polymer solutions, by varying certain parameters of an electrospinning apparatus and/or the solutions used therewith.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to (a) U.S. Provisional PatentApplication No. 61,713,785 by Pham et. al. entitled “Systems and Methodsfor Facilitating the Generation of Core-Sheath Taylor Cones inElectrospinning” filed Oct. 15, 2012, and (b) U.S. Provisional PatentApplication No. 61/723,882 by Pham et al. entitled “Systems and Methodsfor Facilitating the Generation of Core-Sheath Taylor Cones inElectrospinning” filed Nov. 8, 2012. The entire disclosure of each ofthe foregoing references is incorporated by reference herein for allpurposes.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with Government support under 70NANB11H004awarded by the National Institute of Standards and Technology. TheGovernment has certain rights in the invention.

TECHNICAL FIELD

The present invention relates to systems and methods for themanufacturing of microscale or nanoscale concentrically-layered fibersby electrospinning, and more particularly to systems and methods forfacilitating the initiation and stabilization of core-sheath Taylorcones during electrospinning.

Macro-scale structures formed from concentrically-layered nanoscale ormicroscale fibers (“core-sheath fibers”) such as AxioCore® fiberscommercialized by Arsenal Medical (Watertown, Mass.) are useful in awide range of applications including drug delivery, tissue engineering,nanoscale sensors, self-healing coatings, and filters. On a commercialscale, the most commonly used techniques for manufacturing core-sheathfibers are extrusion, fiber spinning, melt blowing, and thermal drawing.None of these methods, however, are ideally suited to producingdrug-loaded core-sheath fibers, as they all utilize high temperatureswhich may be incompatible with thermally labile materials such as drugsor polypeptides. Additionally, fiber spinning, extrusion andmelt-blowing are most useful in the production of fibers with diametersgreater than ten microns.

Core-sheath fibers with diameters less than 20 microns can also beproduced by electrospinning, in which an electrostatic force is appliedto a polymer solution, to induce the formation of electrospinning jetswhich harden to form very fine fibers. Conventional electrospinningmethods utilize a needle to supply a polymer solution, which, uponactivation of an electric field, is then ejected into a continuousstream toward a grounded collector. As the jet stream travels in theair, solvent evaporation occurs resulting in a single long polymerfiber. Core-sheath fibers have been produced by electrospinning usingcoaxial needles, in which concentric needles are used to eject differentpolymer solutions: the innermost needle ejects a solution of the corepolymer, while the outer needle ejects a solution of the sheath polymer.

Coaxial electrospinning has been used in the fabrication of core-sheathfibers for drug delivery in which the drug-containing layer (the “core”)is confined to the center of the fiber and is surrounded by a drug-freelayer (the “sheath”). The sheath then serves as a diffusion barrier to atherapeutic agent in the core. Thus, release rates of the drug can betightly controlled by varying the thickness, composition, anddegradation profile of the sheath material as well as composition andconcentration of the drug in the core. Additionally, core-sheath fiberscan be used for tissue engineering (e.g., incorporation of therapeuticsto affect cell growth), filtration (e.g., by incorporation ofself-cleaning compounds such as titanium dioxide), sensors (e.g.,creation of hollow fibers to allow measurement of small analytevolumes), and as self-healing materials (e.g., spontaneous repair ofsurfaces with release of core contents). Core-sheath fibers can also beused as a way to create fibers from materials that would be otherwiseunable to be electrospun (e.g., polymer pre-cursors such aspoly(glycerol sebacic acid) or insulating materials such as Teflon). Todo so, the material incompatible with electrospinning is confined in thecenter of the fiber and is surrounded by a material optimized torelectrospinning; upon completion of the process the surrounding sheathmaterial is removed (e.g., dissolved or melted away).

The use of a conventional coaxial needle electrospinning apparatus isdepicted in FIG. 1A. The two concentric needles 110 separately deliverthe core and sheath solutions—the core solution is delivered through theinner needle 112 whereas the sheath solution is delivered through theouter needle 114. A grounded collector (not shown) is placed at adistance from the needle, and a potential is generated between thecollector and the concentric needles 110 with a magnitude and directionsufficient to impel both solutions from the needles in a continuousstream toward the grounded collector. Each stream forms a singlecore-sheath fiber, so the throughput of coaxial electrospinning methodsis inherently limited by the fact that only one stream can be producedby each concentric needle pair 110.

To increase throughput, coaxial nozzle arrays have been utilized, butsuch arrays pose their own challenges, as separate nozzles may requireseparate pumps, the multiple nozzles may clog, and interactions betweennozzles may lead to heterogeneity among the fibers collected. Anothermeans of increasing throughput, which utilizes a spinning drum immersedin a bath of polymer solution, has been developed by the University ofLiberec and commercialized by Elmarco, S.R.O. under the markNanospider®. The Nanospider® improves throughput relative to otherelectrospinning methods, but to date core-sheath fibers have not beenfabricated using the Nanospider®.

A high-throughput approach for generating the core-sheath fibers, whichhas beat commercialized by Arsenal Medical (Watertown, Mass.) (the“Arsenal Electrospinning Technology”), utilizes a plurality of elongatevessels with narrow apertures or slits which are aligned to co-localizedifferent materials to multiple sites that form Taylor cones, therebypromoting the formation of multiple electrospinning jets and electrospunfibers with high throughput, as discussed in. e.g., U.S. patentapplication Ser. No. 13/362,467, filed on Jan. 31,2012 (U.S. Patent App.Pub. No. 2012/0193836). the entire disclosure of which is herebyincorporated by reference.

FIG. 1B depicts an apparatus 120 implementing the ArsenalElectrospinning Technology. The apparatus 120 includes an elongatevessel 22 having one or more elongate apertures or slits 124 extendingalong at least a portion of the vessel 122; each slit surface includesone or more slits 126. A positive terminal of a power supply (not shown)is connected to the elongate vessel 122 directly or via a wire such thata potential difference exists between the elongate vessel 122 and agrounded collector 128. Upon application of a voltage, the core polymersolution 130 becomes charged; the charged polymer solution is acted uponby an electrostatic force impelling the core polymer solution 130 awayfrom the elongate vessel 122 that counteracts the surface tensionthereof. When the applied voltage is above a critical threshold value,Taylor cones 132 and electrospinning jets (or jets) 134 form at theexposed slit surfaces; the jets 134 are then attracted toward thecollector 128, thereby forming homogeneous fibers.

The Arsenal Electrospinning Technology facilitates the manufacture ofcore-sheath fibers at high throughput by allowing significantly largervolumetric flow rates relative to needle-based systems 132, thusaddressing a long-standing need in the field for efficient,high-throughput production of electrospun core-sheath fibers. However,further improvements in the efficiency of the Arsenal ElectrospinningTechnology could facilitate the use of core-sheath fibers in manyapplications, and could potentially significantly reduce the cost ofproducing such fibers.

SUMMARY OF THE INVENTION

The present invention, in its various embodiments, addresses theever-present need in the field for increased efficiency in core-sheathfiber production by providing improved systems and methods forhigh-throughput production of electrospun core-sheath fibers.Embodiments of the invention improve the consistency of core- andsheath-polymer incorporation into Taylor cones and/or electrospinningjets and electrospun fibers by optimizing shear stresses applied atfluid boundaries between core- and sheath-solutions at sites of Taylorcone initiation.

In one aspect, the invention relates to a method for forming anelectrospun core-sheath fiber that includes providing an apparatus thatincludes first and second vessels defining first and second elongateapertures, respectively, which are aligned with one-another. Theapparatus also includes a grounded collector at a distance from theapertures. According to embodiments of the invention, a first flowablematerial comprising a core polymer and a second flowable materialcomprising a sheath polymer are flowed into the first and secondvessels, then an electrical potential is created between the aperturesand the grounded collector, with potential sufficient in magnitude andorientation to initiate and sustain multiple electrospinning jets. Themethod also includes optimizing a shear stress generated at a fluidinterface such that a desired ratio of core to sheath polymer isachieved in the resulting electrospinning jets; this optimization occursthrough the selection of appropriate parameters such as length or widthof the first and/or second apertures and velocity or viscosity of thefirst and/or second flowable materials. In various embodiments, thefirst flowable material exits the first aperture at a first velocity,while the second flowable material exits the second aperture at a secondvelocity, and the first velocity can be about 1.3 times, 2.25 times or2.5 times greater than the second velocity, and may vary during theapplication of the electrical potential. In some cases, the first andsecond elongate apertures are nested and aligned along a single centralaxis, and the width of the first aperture is optionally about half ofthe width of the second aperture. The first and second elongateapertures can have the same length, or they may have different lengths.The first vessel is optionally nested inside of the second vessel, inwhich case the first and second apertures are parallel so that materialthat is ejected from the first aperture must also pass through thesecond aperture on the way to the collector. The first and secondapertures are in certain embodiments of the method, co-planar, while inother instances they are offset by about 1 mm, in which case the firstvessel and the first aperture are optionally submerged in the secondflowable material. In some cases, the first and second flowablematerials are characterized by particular viscosities, and the firstflowable material is less viscous than the second flowable material.

In another aspect, the invention relates to an apparatus forhigh-throughput electrospinning of core-sheath fibers that includesfirst and second elongate vessels having first and second elongateapertures, respectively. The first and second elongate apertures arealigned about a single central axis, each of the vessels is in fluidcommunication with a fluid source that is optionally filled with firstand second flowable materials comprising a core and a sheath polymer,respectively, and the apparatus includes a plurality of valves or othercontrol means for providing the first and/or second flowable materialsat predetermined races. In some cases, the first and second vessels arenested, and the apparatus includes means for adjusting a height of thefirst vessel and the first aperture relative to the second aperture,thereby controlling the depth at which the first vessel and the firstaperture are submerged within the second flowable material in the secondvessel. In some instances, the first and second vessels arewedge-shaped, and the elongate apertures are positioned at apexes of thevessels.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be described byway of example with reference to the accompanying figures, which areschematic and are not intended to be drawn to scale. In the figures,each identical or nearly identical component illustrated is typicallyrepresented by a single numeral. For purposes of clarity, not everycomponent is labeled in every figure, nor is every component of eachembodiment of the invention shown where illustration is not necessary toallow those of ordinary skill in the art to understand the invention, inthe figures:

FIGS. 1A-1B include schematic illustrations of examples ofelectrospinning setups;

FIG. 2 includes an exemplary schematic illustration of an embodiment ofthe invention;

FIGS. 3A-B include examples of controlling the generation of core-sheathTaylor cones to facilitate the formation of core-sheath fibers.

FIGS. 4A-4D include exemplary schematic illustrations of an embodimentof the invention wherein flow rates of material to the core slit andsheath slit surfaces are different to form a core-sheath fiber.

FIGS. 5A-C include exemplary schematic illustrations of embodiments ofthe invention wherein fixture variables are changed to form core-sheathfibers, including slit width, core and sheath flow velocity, and lengthof core and sheath slits.

FIGS. 6A-D illustrate some embodiments wherein the sheath flow rate ishigher than the core flow rate.

FIGS. 7A-D illustrate core sheath fibers as formed by the embodiments ofthe invention with a drug core enclosed by a polymer sheath.

FIGS. 8A-F illustrate some embodiments where the core solution flowrates and velocities are varied.

FIGS. 9A-D illustrate some embodiments of the invention with differentsheath and core slitwidths.

FIG. 10A includes exemplary schematic illustrations of embodiments ofthe invention wherein the depth of the core slit surface varies relativeto the sheath slit surface.

FIG. 10B shows taylor cones generated in the embodiments depicted inFIG. 10A.

FIG. 11 illustrates some embodiments of the invention wherein materialviscosity is varied to form core-sheath fibers.

FIG. 12A-D illustrates fibers and patches formed according to methods ofthe invention.

DETAILED DESCRIPTION

FIG. 2 illustrates a top view of one embodiment of a system thatgenerates core-sheath fibers using a needleless, core-sheathelectrospinning process. The core and sheath solutions are firstdelivered to a slit surface; at the slit surface, a fluid meniscus formsand numerous electrospinning jets may initiate at one or more slits uponactivation of an external electric field. In various embodiments,controlling the generation of core-sheath Taylor cones at the fluidmeniscus facilitates the formation of core-sheath fibers. For example,upon generating distinct Taylor cones, as shown in FIG. 3A, in theneedleless electrospinning process, core-sheath jets and fibers aresubsequently created.

FIG. 4A-4D schematically depict core and sheath polymer solutionsdelivered to the core and sheath slits, respectively, through therespective features using, for example, syringe pumps. In oneembodiment, the flow rate of the sheath solution that fills the left andright channels is relatively faster than that of the core solution (FIG.4A); as the sheath solution from the two channels merges at the top ofthe slit surface and bridges the gap therebetween, a fluid meniscus iscreated under the force of surface tension (FIG. 4B). Upon applying apotential voltage to the slit fixtures, the sheath polymer solutionbecomes charged; the induced charges may accumulate on the outer surfaceof the sheath solution (FIG. 4C). As a result, sheath jets may beinitiated when a critical potential has been reached. In addition, thepressure of the internal core fluid at the locations where the sheathsolution jets are formed may drop allowing the core fluid to be pulledby the applied electric field (FIG. 4C). Because the internal coresolution flows towards locations having a relative lower pressure, underthe shear forces of the sheath solution, a core-sheath Taylor cone maybe generated (FIG. 4D).

In various embodiments, the formation of the core-sheath Taylor conesand/or jets is controlled via the manipulation of various parameterswhich control the shear stress between the sheath and core solutions.The shear stress may be varied by changing the geometry of the slitfixtures, velocities, or viscosities of the core and/or sheathsolutions. For example, if the flow velocity of the sheath solution isgreater than that of the core solution at the exit point of the slitsurfaces, distinct core-sheath Taylor cones may be formed. The flowvelocities of the solutions depend on the volumetric flow rates and thesurface areas, as given in Equations (1) and (2), where Q_(sheath) andQ_(core) represent the flow rates of the sheath and core solutions,respectively; d_(sheath) and d_(core) are the widths of the sheath andcore slits, respectively, and L_(sheath) and L_(core) are the lengths ofthe sheath and core slits, respectively (as shown in FIG. 5).Accordingly, the flow velocities of the sheath and/or core solutions maybe manipulated by changing the volumetric flow rates and/or the slitgeometries thereof.

$\begin{matrix}{v_{total} = \frac{Q_{sheath} + Q_{core}}{d_{sheath} \times L_{sheath}}} & (1) \\{v_{core} = \frac{Q_{core}}{d_{core} \times L_{core}}} & (2)\end{matrix}$

In various embodiments, the flow velocities of the sheath and coresolutions are varied based on the variations in the flow rates thereofwhile maintaining the slit geometry. In one embodiment, the slit-fixtureis comprised of two triangular shaped hollow troughs that are aligned toa single vertical plane to form a one-dimensional slit-surface (FIG. 2)The lengths of the sheath and core slits are 41 mm and 35 mm,respectively, and the widths of the sheath and core slits are 2.2 mm and0.6 mm, respectively. Referring to Table 1, in one embodiment, the coreflow rate is set constant (e.g., at 20 mL/h) while the sheath flow rateis varied from 20 mL/h to 200 mL/h to manipulate the formation of theTaylor cones (Note: The conditions used in this and experimentsfollowing corresponds to flow rates of up to 300 ml/h, resulting insignificantly higher volumetric throughput relative to needle-basedsystems). As shown in FIG. 6A-D, the most distinct core-sheath jets (asvisualized by a clear delineation between the core and sheath solutionsin the Taylor cone due to the presence of dexamethasone in the core)occur for condition A where the sheath flow-rate is ten times largerthan the core flow rate (or the total velocity is approximately 2.5times greater than the core velocity); whereas no distinct core-sheathjets are discernible for condition D where the sheath flow rate isroughly the same as the core flow rate (or the total velocity isapproximately 2.25 times less than the core velocity). Accordingly,varying the sheath flow rate and thereby changing the relative ratio ofthe sheath solution velocity to core solution velocity effectivelyfacilitates the formation of the core-sheath Taylor cones; a higherlikelihood of generating the Taylor cones occurs when a ratio of thesheath flow velocity to the core flow velocity is larger.

FIGS. 7A-D depict typical fibers that are produced using the systemdescribed above. The diameter of the fibers are approximately 2-4micron, which is within the order of magnitude expected for electrospunfibers. FIGS. 7A-D also include scanning electron micrographs of fibercross-sections illustrating the encapsulation of dexamethasone within asheath polymer.

Core Flow Rate

Referring to Table 2, in another embodiment, the sheath flow rate iskept constant while the core flow rate is varied. Specifically, thesheath flow rate was set to 200 ml/h while the core flow rate wasmodulated from between 20 to 100 ml/hr. The same polymer solutions wereused, as described previously. Again, when the sheath flow velocity isgreater than the core solution flow velocity, the core-sheath Taylorcone formation has a higher probability of being distinct (FIGS. 8A-F).In another embodiment, the core flow rate was kept constant at 20 ml/hrand the sheath flow rate was varied from 200 ml/hr (forming a distinctcore-sheath) to 100 ml/hr (forming a distinct core-sheath) to 40 ml/hr(forming a non-distinct core-sheath.

The core-sheath fiber formation may thus be manipulated by varying ofthe flow rates of the sheath and/or core solutions.

Slit Fixture Geometry Core Slit Width

As shown in Eqs. (1) and (2), the velocities of the core and sheathsolutions depend on the slit fixture geometry (e.g., the widths and/orlengths of the core and/or sheath slits). In various embodiments, thelengths of the sheath and core slits (i.e., L_(sheath) and L_(core),respectively) are approximately equal such that the formation of theslits across the entire fixture is the same in order to reduce themanufacturing complexity. As a result, the widths of the sheath and coreslits are the primary variables in the slit geometry that may be alteredto manipulate the flow velocities of the solutions. In one embodiment,the width of the core slit is varied while that of the sheath slit isfixed at 2.2 mm; the sheath flow rate is set to be constant at 200 ml/hwhile the core flow rate is adjusted as listed in Table 3. As indicatedin Eq. (2), the core flow velocity is greater in a narrower core slit ata given core flow rate also shown in the shaded squares of Table 3).Because the core-sheath jets are formed when the velocity of the coresolution is smaller than that of the sheath solution, the maximum coreflow rate that may be able to generate distinct core-sheath Taylor conesfor a narrower core slit is smaller than that of a wider core slit. Forexample, referring to Table 3, a core flow rate of 5 mL/h is sufficientfor a core slit having a width of 0.3 mm to form distinct Taylor cones,whereas a core flow rate of 20 mL/h is required to form distinct Taylorcones for a core slit having a width of 0.9 mm. The width of the coreslit may further impact the flow of the sheath solution. For example,utilization of the 0.9 mm-wide core slit may leave little space for thesheath fluid flowing through the 2.2 mm-wide sheath slit (because thewall thickness of the core slit may be as thick as 0.3 mm). Accordingly,in one embodiment, the core slit width is carefully chosen such that theflow of the sheath fluid is not impeded.

Sheath Slit Width

In another embodiment, the width of the sheath slit varies from 1.5 mmto 3 mm while the width of the core slit is fixed at 0.6 mm and the flowrates of the sheath and core solutions are set constant at 200 mL/h and20 ml/h, respectively. Again, because the core-sheath jets are formedwhen the velocity of the sheath solution is larger than that of the coresolution, the minimum sheath flow rate capable of generating distinctcore-sheath Taylor cones for a wider sheath slit is greater than that ofa narrower sheath slit, as shown in Table 4. Note that the velocity ofthe sheath solution being greater than that of the core solution isnecessary for formation of the core-sheath Taylor cones; this, however,may not be the only criteria. For example, a larger difference betweenthe sheath and core velocities may result in easier formation of thedistinct core-sheath cone and/or jet structure.

Theoretically, the maximum electric field (E) attainable for a wedgeshaped conductor depends upon the slit width (d), and wedge angle (α),as described by Eq. 3, where V₀ is the applied voltage and R is adistance above the jet. Equation (3) indicates that the electric fieldis inversely proportional to the width of the slit. Table 5 depicts thata wider sheath slit may result in lower jet stability at a constantvoltage (e.g., 85 kV); this agrees with the theoretical prediction thatthe slit geometry may affect the stability of core-sheath jet induced bythe electrical field. A higher voltage may be required to produce stablejets when wider slits are employed. Referring to Table 6, in variousembodiments, when a wider sheath slit is used, a higher voltage isrequired to generate a larger number of stable jets.

$\begin{matrix}{E \sim {\frac{V_{0}}{R}\left( \frac{R}{d} \right)^{{x/\alpha} - 1}}} & (3)\end{matrix}$

Sheath Slit Width and Core Slit Width

In various embodiments, the widths of the sheath and core slit fixturesare both varied, e.g., reduced to 1.5 mm and 0.3 mm, respectively. Theflow rates of the sheath and core solutions may also be changed suchthat the flow velocities thereof remain die same as that of thesolutions flowing in slits having larger width dimensions (e.g., sheathslit width of 2.2 mm and core slit width of 0.6 mm). For example, asshown in Table 7, the flow rates of the sheath and core solutions arechanged to 140 mL/h and 10 mL/h, respectively, in the smaller slits(i.e., sheath slit width of 1.5 mm and core slit width of 0.3 mm) tomatch the flow velocities of 0.68 mm/s and 0.27 mm/s of the sheath andcore solutions, respectively, generated using larger slits (i.e., sheathslit width of 2.2 mm and core slit width of 0.6 mm) and greater flowrates (i.e., 200 mL/hr and 20 mL/hr for the sheath and core solutions,respectively). These results indicate that electrospinning apparatusdesign parameters in general, and specifically a smaller sheath slitarea or larger core slit area, can affect the quality of sheath and/orcore solution into Taylor cones and/or electrospun fibers. Withoutwishing to be bound by any theory, it is believed that modifying therelative areas of the core and/or sheath slits can result in highersheath velocities relative to core velocities for a given core or sheathflow rate. This in turn enables the formation of core-sheath fiberswhere the core flow rate is higher and, therefore, the core makes up alarger proportion of the fiber for elcctrosprayed particle)cross-sectional area, diameter or volume. Again, the formation of thecore-sheath Taylor cones occurs when the total velocity is relativelygreater than the core velocity; this is applicable to slit fixtureshaving various slit widths (FIGS. 9A-D). Note that Taylor cones are notobservable for condition D of Table 7, even though the sheath flow rateis much greater than the core flow rate; this again indicates that it isthe velocity difference, not the flow rate difference, between the coreand sheath solutions that controls the formation of the cote-sheathfibers.

Core Slit Height

Referring to FIG. 10A, in some embodiments, the height spacing betweenthe apex of the core and sheath slit fixtures varies from 1 mm to 6 mm.Using sheath and core flow rates of 200 and 20 ml/h, respectively, andan applied voltage of 75 kV, a larger spacing resulted in less distinctcore-sheath Taylor cones, as shown in FIG. 10B; this indicates that anoptimal core and sheath slit spacing exists that benefits the shearforces applied on the core fluid by the sheath fluid to producesuccessful viscous entrainment.

Viscosities of the Solutions

Variations in the fluid properties (e.g., viscosity) of the core and/orsheath solutions may result in significant changes to the shear stress,thereby affecting the formation of the core-sheath Taylor cones. Invarious embodiments, the viscosity of the sheath solution is varied, forexample, by adjusting the weight percentage of PCL solution. Referringto Table the viscosity of the sheath solution changes from approximately280 cP to 760 cP when the PCL content in 6:1 (by vol) CHCl₃:MeOH ischanged from 12 wt % (system C) to 16 wt % (system D), respectively; theviscosity of the core solution is fixed at roughly 500 cP in bothsystems. In one implementation, the core flow rate varies from 5 mL/hrto 20 mL/hr and the flow rate of the sheath solution is kept constant at200 mL/h. As shown in FIG. 11, at the same flow rate conditions, thecore-sheath formation and morphology of the Taylor cones is moredistinct when the viscosity of the sheath solution is larger than thatof the core solution (system D). Again, generation of the distinctTaylor cones is facilitated in the systems having a larger viscosity ofthe sheath solution compared with that of the core solution.Accordingly, generation of the Taylor cones and formation of the fibersmay be manipulated via both flow velocities and fluid viscosities of thesolutions. Note that although the viscosity of the sheath solution istuned by adjusting the weight percentage of PCL, one of ordinary skillin the art will understand that the viscosity of the sheath and/or coresolution may be adjusted using other approaches, such as heating andcooling of the solutions or utilization of polymers having differentmolecular weights.

Core Sheath Fiber Applications

The invention described herein can be used to manufacture any type ofcore sheath structure that is traditionally fabricated via a needlesetup. Broadly speaking, core-sheath electrospinning is employed insituations to: (1) create bicomponent fibers: (2) to encapsulate aparticle; (3) to create fibers from traditionally unelectrospinnablematerials; (4) to create hollow fibers. These types of fibers haveapplications in a variety of fields including drug delivery, tissueengineering, diagnostics, electronics, energy storage, textiles, etc.

Bicomponent fibers fabricated using core-sheath electrospinning containa core material that is different than the sheath material. This isdesirable in instances where it is desired to combine the properties oftwo different types of polymers into a single fiber. These propertiescan be mechanical, chemical, biological, degradation, solubility, etc.in nature. For example, a core-sheath fiber consisting of PCL as thecore and collagen as the sheath relies on the PCL component to impartmechanical integrity to the fiber while the collagen (being biological)imparts biocompatibility when implanted in vivo. Another example isbicomponent fibers with different solubility characteristics whereineither the core or the sheath acts as a sacrificial layer (this methodcan also be used to create hollow fibers—see below). In another example,bicomponent fibers with piezoelectric properties can be made with PVDFsheath and an intrinsically conductive polymer core. Alternatively, thebicomponent fibers can consist of a solid sheath but contain a non-solidcore (e.g. liquid). In another embodiment, the components of the sheathand the core in the biocomponent fiber can react during electrospinningor after fibers have formed. Bicomponent fibers are also useful insituations whereby cost of materials is an issue. For example, lessexpensive material can be used in the core while a more expensivematerial is used in the sheath. This allows less sheath material to beused, thus conserving costs. Another example is bicomponent fibershaving a biodegradable core material (e.g., PLGA inhexafluoroisopropanol electrospun at a flow rate of 40 ml/hr) and abiostable sheath material (e.g., nylon 6,6 in hexafluoroisopropanolelectrospun at a flow rate of 200 ml/hr), as shown in FIG. 14.

Core-sheath fibers can be used to encapsulate any particle, either indissolved or particulate form. Any number of particles, biologic,organic, organometallic, ceramic, and inorganic compounds cantheoretically be encapsulated and include but are not limited to thefollowing: small molecule chemicals, proteins, fluorophores, metals,hydrides, microparticles, plastics, carbon black, carbon nanotubes,graphene, flutopolymers (e.g.:Teflon), liposomes, etc.

Using core-sheath electrospinning, materials that are traditionallyunelectrospinnable can be co-electrospun into fibers using a polymerthat is electrospinnable. The unelectrospinnable material can exist as acomponent in the resulting bi-component fiber system or theelectrospinnable material can be removed after fiber fabrication,leaving behind only the unelectrospinnable material. Theunelectrospinnable material can either be in the sheath or the core.Depending on the unelectrospinnable material can be used to coat a corecarrier polymer, as described below with Teflon AF. Examples ofunelectrospinnable materials include resins, latent curatives, phasechange materials, certain inherently conducting polymers, solgels,Teflon AF, and prepolymers and thermosetting polymers that requirecross-linking such as PGS, PPF, PLCL, PGCL, PDMS, and/or polyurethanes,polyesters, polyimides, epoxies, and the like. An example in which theunelectrospinnable material is the sheath is with Teflon AF. Teflon AFby itself is unelectrospinnable due to low conductivity of the solution;however, using a core carrier polymer such as PCL, core sheath fiberscan be fabricated that consist of the core polymer being coated by theTeflon AF. In other instances, the unelectrospinnable material isincorporated into the core. For example, a core-sheath fiber thatconsists of a prepolymer in the core. Once the fibers are formed, thefiber is subjected to the curing step (e.g. heat, UV, etc), that resultsin the prepolymer cross-linking and becoming solid. The sheath materialcan then be removed if desired, to leave behind the core polymer as afiber. An example of this is with PDMS, which can be electrospun in thecore with a polymer sheath. After fabrication, the fibers can then beexposed to heat allowing for the PDMS to cure and harden, forming abicomponent fiber of PDMS and sheath polymer. The polymer sheath canthen be removed if desired (e.g. by dipping in solvent), to leave behindPDMS fibers. In an alternate embodiment, the unelectrospinnable materialcan be used to influence the formation and resulting quality of thefibers that are produced. For example, an unelectrospinnable saltsolution can be used as the sheath in order to help drive down the fiberdiameter of the core polymer that is electrospun. In an example of usingthe present invention to electrospin materials that are traditionallyunelectrospinnable, a core-sheath fiber was made with a sheath polymersystem of 3.5 w t% 85/15 PLGA in 6:1 (by volume) chloroform:methanol,and a core polymer of PDMS (Sylgard 184, a two-part liquid systemconsisting of a pre-polymer and a cross-linking agent mixed in a 10:1mass ratio), as shown in FIG. 12C. The sheath and core solution flowrates were 200 ml/hr and 20 ml/hr. respectively. The fibers were spuninto a mesh approximately 1 mm in thickness, which was placed in an overat 100° C. for three hours. To optionally yield a homogeneous fiber(i.e., a fiber that is not core-sheath, but instead a singlecross-sectional structure) as shown in FIG. 17, the mesh was immersed inchloroform for one hour to allow the PLGA sheath to dissolve to yieldPDMS fibers. In alternative embodiments of forming PDMS fibers,water-soluble polymers such as PEO, PVA, gelatin or dextran are used forthe sheath material, which is removed from the electrospun fibers usingaqueous means. In other alternative embodiments, other two-part PDMSsystems can be cured by exposure to UV light or cross-linked intoelastomers through free radical, condensation, or other reactions; orone-pan PDMS can be used that cure upon exposure to moisture in theatmosphere or upon photocuring. In other alternative embodiments, thesheath is removed by degradation instead of solvent dissolution, or isetched away using an acid or other etchant, or if sufficiently brittle,is mechanically disrupted to fracture and separate the sheath from thecore.

Core-sheath fibers can be used to create hollow fibers. Hollow fiberscan be efficient as air filled fibers for clothing insulation. As well,the temporary nature of the core can allow for sufficient reinforcementof the material for weaving or post-processing and upon removal, leavebehind ultralight but strong fabrics. Biomedical, electronic, optical,sensing, energy storage, and catalysis applications, for example) canutilize hollow fibers, which have excellent insulative properties.Hollow fibers can allow for better nutrient and gas exchange for tissueengineering applications. Hollow fibers can be created using oil as thecore and after fabrication, removal of the oil by extraction in solventssuch as octane or hexane. Hollow ceramic (e.g,, SiO2, SnO2, Al2O3, ZnOand TiO2) fibers via sot-gels of their alkoxide precursors can also beelectrospun into hollow fibers. Alternatively, hollow fibers can also becreated by using a water soluble or biodegradable polymer in the coreand a non-water soluble or biostable polymer as the sheath. Subsequentextraction in water or exposure in vivo will remove the aqueous-solublecore. In general, hollow fibers can be created from core-sheath fibersin which the core material dissolves in the extraction solvent, whereasthe sheath material does not. An example of this concept was carried outusing 2 wt % polyethylene oxide (PEO) in 6:1 (by volume)chloroform:acetonitrile as the core material and 3.5 wt % PLGA inhexafluoroisopropanol as the sheath material. The sheath flow rate was200 ml/hr while the core flow rate was 20 ml/hr, using the slit-surfaceneedleless electrospinning system. The water-soluble PEO core wassubsequently dissolved to yield a hollow PLGA fiber, as shown in FIG.12B. In other example, PLGA is used for the core material and nylon inthe sheath, followed by the use of chloroform to dissolve the PLGA toyield hollow nylon fibers.

The systems and methods described herein can be modified to novelelectrospun or electrosprayed articles. In one example, the polymersolutions described above are diluted, such that core-sheath micro ornanoparticles are generated at high throughput by electrospraying. Inanother example, the core and/or sheath solutions supplied to anelectrospinning apparatus are generated by melting, rather thandissolving, a polymer composition. In still another example, differentcore and/or sheath solutions are delivered to different segments alongthe length of the slit, thereby forming, in a single apparatus, at leasttwo different fiber types characterized by different core and/or sheathcompositions, and facilitating the generation of higher-order structuressuch as yarns, ropes, or patches that incorporate the different fibertypes.

Other embodiments include a sheath material with a lower melting pointthan the core material such that heating a mesh of electrospun fibersresults in melting of the sheath material (but not the core material) atthe fiber cross-over points in the mesh without compromising theintegrity of the overall mesh.

Still other embodiments make use of a sheath material that has theability to absorb or repel water of other fluids while the core materialprovides mechanical integrity.

The systems and methods described above are used, in some instances, tocreate very small (nm) diameter-sized fibers, which are otherwisedifficult to produce. This can be achieved, for example, by having ahigh sheath flow rate relative to the core flow rate, resulting in acore-sheath fiber with a very small core. Upon sacrificial removal ofthe sheath layer, the small core filler remains.

The fibers of the present invention have numerous applications inmedicine. For example, fibers and meshes of the present invention can beused as supports for rotator cuff repair or similar orthopedicapplications at the tissue/suture interface; as protein microarrays withlow limits of detection due to increased surface area with fibers; asnovel hydrophobic filters that are thermostable; as water-repellant butbreathable lightweight fabric; as medical bandages for burns or woundsthat allow gas exchange and exudates to fill the porosity therein; astissue engineering scaffolds; as drug delivery vehicles; as sensors anddiagnostic elements; as self-healing coatings; as filter elements; astextiles; in clean tech applications; and in numerous other medical andnon-medical applications.

The fibers of the present invention may be fabricated by a wide range ofpolymeric materials, as described herein. Examples not previouslyidentified include a core-sheath fiber structure formed from a sheathmaterial of 85/15 L-PLGA in chloroform:methanol and a core material of70/30 PCL/dexamethasone in chloroform:methanol (where PCL ispolycaprolactone, and the core material may or may not include atherapeutic agent); sheath materials of 12 wt % PCL and 16 wt % PCL inchloroform:methanol and a core material of 12 wt % PCL in 6:1 (byvolume) chloroform:methanol containing 30 wt % dexamethasone relative toPCL.

Advantages of the Invention as it Relates to High Throughput Open-BathMonofiber Fabrication Systems

Current high throughput methods to create mono fibers utilize a rotatingdrum or wire bundle mostly immersed in an open bath of polymer solution,or free surface electrospinning. The operation requires that thesolution have an optimal viscosity and surface tension such thatsolution can be drawn up onto the surface of the drum or wire as itrotates. The open nature of the bath solution results in an inherentlimitation in which solvent evaporation occurs, resulting in the polymersolution becoming more viscous over time. The closed-system of theneedleless system docs not have this inherent disadvantage of solventevaporation. The requirement of viscosity along with solvent evaporationcan potentially limit the versatility of polymer/solvent systems thatcan be electrospun using these methods. For example, certainsolvent/polymers potentially cannot be electrospun because theevaporation rate is too quick or they do not impart rheologicalproperties amenable to being drawn up onto the drum surface.

The solution viscosity that works with open bath free surfaceelectrospinning systems are relatively lower than that used with theneedleless fixture described herein. Thus, electrospinning of polymersuspensions will be more difficult, due to more settling of theparticles in less viscous solutions. It is also less likely that aparticle with weight can be dragged up onto the surface of the rollingdrum. Additionally, our needleless setup is capable of electrosprayingsolutions.

Another advantage of our system relative to the open bath free surfacesystem is that there is no material waste because all of the polymersolution can be pushed through the slit fixture and electrospun intofibers. This is not possible in the case of open bath systems, whichrequires the rotating mandrel to be rotating in a bath of solution inorder for fibers to be formed. Therefore, there will always be materialthat is not consumed. Moreover, the efficiency of solution consumptionof the disclosed invention relative to the open bath system should begreater in the needleless fixture. The amount of solution-material thatis consumed (electrospun) per unit of time using the drum and open bathis relatively less than the amount that can be consumed in the sameamount of time via the needleless fixture described herein, since only athin layer of solution is drawn up during each rotation and not all ofthe solution is electrospun.

The operation of the open bath free surface electrospinning requiresthat spinning and subsequent fiber collection occurs upwards. Our systemis capable of electrospinning and fiber collection in any direction. Forexample, using our process, fiber collection can occur upside-down. Thiscan be beneficial in circumstances in which one would want to collectfibers downwards towards/into a bath of water for example.

In electrospinning, each Taylor cone that forms leads to one longcontinuous fiber that gets collected. In a typical operation of theneedleless fixture, there are approximately 10 jets that form along thelength of the slit; the collected mesh is therefore comprised of 10 verylong fibers intertwined with one another. In contrast, during theoperation of the open bath free surface electrospinning, hundreds ofjets form and disappear with each rotation of the drum, thus theresulting mesh consists of thousands of relatively short fibers. Thismay result in relatively mechanically weaker meshes compared to lessnumber of longer fibers that are intertwined.

The fibers that are produced using the open bath system arise fromTaylor cones that spontaneously form. Thus, the fiber diameter is likelyto be primarily a function of the solution properties only. The designof the needleless fixture contains processing parameters thatpotentially enable greater control over fiber diameter. For example, inaddition to the solution properties, solution flow rates can hemanipulated to control fiber diameter size. Furthermore, the number ofjets produced can also be controlled, which could lead to differences infiber diameter size.

Another potential advantage of the needleless invention described hereinrelates to maintenance of sterility. The open bath nature of currenthigh throughput electrospinning methods is more easily susceptible tocontamination front particles or fibers that are not collected properly.Conversely, the closed system of our invention mitigates any of theseconcerns.

The phrase “and/or,” as used herein should be understood to mean “eitheror both”of the elements so conjoined, i.e., elements that areconjunctively present in some cases and disjunctively present in othercases. Other elements may optionally be present other than the elementsspecifically identified by the “and/or” clause, whether related orunrelated to those elements specifically identified unless clearlyindicated to the contrary. Thus, as a non-limiting example, a referenceto “A and/or B,” when used in conjunction with open-ended language suchas “comprising” can refer, in one embodiment, to A without B (optionallyincluding elements other than B); in another embodiment, to B without A(optionally including elements other than A); in yet another embodiment,to both A and B (optionally including other elements); etc.

As used in this specification, the terms “substantially/”“approximately” or “about”means plus or minus 10% (e.g., by weight or byvolume), and in some embodiments, plus or minus 5%. Reference throughoutthis specification to “one example,” “an example,” “one embodiment,” or“an embodiment” means that a particular feature, structure, orcharacteristic described in connection with the example is included inat least one example of the present technology. Thus, the occurrences ofthe phrases “in one example,” “in an example,” “one embodiment,” or “anembodiment” in various places throughout this specification are notnecessarily all referring to the same example. Furthermore, theparticular features, structures, routines, steps, or characteristics maybe combined in any suitable manner in one or more examples of thetechnology. The headings provided herein are for convenience only andare not intended to limit or interpret the scope or meaning of theclaimed technology.

The term “consists essentially of” means excluding other materials thatcontribute to function, unless otherwise defined herein. Nonetheless,such other materials may be present, collectively or individually, intrace amounts.

The terms and expressions employed herein are used as terms andexpressions of description and not of limitation, and there is nointention, in the use of such terms and expressions, of excluding anyequivalents of the features shown and described or portions thereof. Inaddition, having described certain embodiments of the invention, it willbe apparent to those of ordinary skill in the art that other embodimentsincorporating the concepts disclosed herein may be used withoutdeparting from the spirit and scope of the invention. Accordingly, thedescribed embodiments are to be considered in all respects as onlyillustrative and not restrictive.

TABLE 1 Variation of the flow rate of the sheath solution Total velocityDistinct Sheath Core greater Core-Sheath Flow Flow Total Core thanTaylor Con- Rate Rate velocity Velocity Core Cones dition (ml/h) (ml/h)(mm/s) (mm/s) Velocity? Formed? A 200 20 0.68 0.27 Yes Yes B 100 20 0.370.27 Yes Yes C 40 20 0.19 0.27 No No D 20 20 0.12 0.27 No No

TABLE 2 Variation of the flow rate of the core solution Total velocityDistinct Sheath Core greater Core-Sheath Flow Flow Total Core thanTaylor Con- Rate Rate velocity Velocity Core Cones dition (ml/h) (ml/h)(mm/s) (mm/s) Velocity? Formed? A 200 20 0.68 0.27 Yes Yes B 200 30 0.710.40 Yes Yes C 200 40 0.74 0.53 Yes Yes D 200 60 0.80 0.80 No No E 20080 0.86 1.06 No No F 200 100 0.92 1.32 No No

TABLE 3 Variation of the width of the core slit

TABLE 4 Variation of the width of the sheath slit Core Slit Width 0.6 mmSheath Slit Width 1.5 mm 2.2 mm 3.0 mm Solution Flow Rates (ml/h) 200:20200:20 200:20 300:20 Total velocity (mm/s) 1   0.68 0.5  0.72 CoreVelocity (mm/s) 0.26 0.26 0.26 0.26 Total velocity > Core Velocity YesYes Yes Yes Quality of core/sheath Taylor Distinct Distinct Not Distinctcone Distinct

TABLE 5 Jet stability at different sheath slit widths (V = 85 kVthroughout) Core Slit Width 0.6 mm Sheath Slit Width 1.5 mm 2.2 mm 3.0mm Solution Flow Rates (ml/h) 100:20 100:20 100:20 Jet Stability HighHigh Low

TABLE 6 Jet number at different sheath slit width Sheath Sheath SheathSheath core Slit = 1.5 mm Slit = 2.2 mm Slit = 3.0 mm flow 40/20 100/20ml/ 40/20 100/20 ml/ 40/20 100/20 ml/ rates ml/hour hour ml/hour hourml/hour hour 90 kV 13 jets 11 jets — — 85 kV 11 jets 11 jets 8 jets 8-9jets 6 jets 4-6 jets 75 kV 10 jets  9 jets 8 jets 8-9 jets —   2 jets 70kV  9 jets — — — — — 65 kV  8 jets — 8 jets 7-8 jets — —

TABLE 7 Flow rates and calculated velocities of slit fixtures havingsmall widths Sheath Distinct Core- Flow Core Flow Total Core Totalvelocity Sheath Taylor Rate Rate velocity Velocity greater than ConesCondition (ml/h) (ml/h) (mm/s) (mm/s) Core Velocity? Formed? A 140 100.68 0.27 Yes Yes B 142 15 0.71 0.40 Yes Yes C 144 20 0.74 0.53 Yes YesD 147 30 0.80 0.80 No No

TABLE 8 Polymer solutions and their viscosities System SolutionViscosity (cP) C - Sheath 12 wt % PCL in CHCl₃:MeOH (6:1 280 vol:vol)D - Sheath 16 wt % PCL in CHCl₃:MeOH (6:1 760 vol:vol) Core solution 12wt % PCL in CHCl₃:MeOH (6:1 500 for both systems vol:vol), 30%Dexamethasone loading relative to polymer mass in core solution

1. A method for electrospinning a core-sheath fiber, comprising thesteps of: providing an electrospinning apparatus comprising a firstvessel having a first elongate aperture, a second vessel having a secondelongate aperture, wherein the first and second elongate apertures arealigned along a single central axis, and a collector positioned at adistance from the first and second elongate apertures; flowing a firstflowable material comprising a core polymer into the first vessel;flowing a second flowable material comprising a sheath polymer into thesecond vessel; adjusting a height of the first vessel and first elongateaperture relative to the height of the second elongate aperture; andapplying an electric potential between the collector and the first andsecond apertures, the electric potential having a magnitude and anorientation effective to form at least one electrospinning jet, whereinat least one parameter selected from the group consisting of a width ofthe first or second aperture, a length of the first or second aperture,and a flow rate of the first or second flowable material is chosen tooptimize a shear stress generated at a fluid interface between the firstand second flowable materials during the application of the potential,such that a desired ratio of core and sheath polymers is incorporatedinto the at least one electrospinning jet.
 2. The method of claim 1,wherein the first flowable material exits the first aperture at a firstvelocity and the second flowable material exits the second aperture at asecond velocity.
 3. The method of claim 2, wherein the second velocityis about 1.3 times greater than the first velocity.
 4. The method ofclaim 2, wherein a ratio of the first velocity to the second velocityvaries during the application of the electric potential.
 5. The methodof claim 1, wherein the first aperture has a first width and the secondaperture has a second width.
 6. The method of claim 5, wherein the firstwidth is about half of the second width.
 7. The method of claim 1,wherein a length of the first elongate aperture is equal to a length ofthe second elongate aperture.
 8. The method of claim 1, wherein a lengthof the first elongate aperture is less than a length of the secondelongate aperture.
 9. The method of claim 1, wherein the materialejected from the first elongate aperture in the at least oneelectrospinning jet passes through the second elongate aperture as well.10. The method of claim 9, wherein the first vessel and the firstelongate aperture are submerged in the second flowable material andwherein adjusting the height of the first vessel and first elongateaperture relative to the height of the second elongate aperture controlsthe depth at which the first vessel and first elongate aperture aresubmerged within the second flowable material in the second vessel.